During shear VWF-dependent platelet adhesion (A), the VWF A1 domain binds first to GPIb; then, after initial tethering, the platelet becomes activated and promotes binding between VWF released from ECs and additional platelets, supporting thrombus formation. In the case of normal HDL/ApoA-I levels, VWF fibers are less extended with the normal size of platelet thrombi (B). In the case of reduced HDL/ApoA-I levels, VWF fibers are longer and thicker and generate larger platelet thrombi (C). These antithrombotic effects of HDL/ApoA-I are reported for the first time. Illustration by Luigi Flaminio Ghilardini, University of Milan.